Principal Investigator: Carlos E. Prada, MD
The RASopathies are a group of disorders with altered proteins relevant for signaling in the RAS-MAPK pathway leading to a variety of clinical features and severity. Clinical diagnosis can present a challenge in patients with mild facial features, absence of congenital heart defects, and young age. Identifying the genes that cause RASopathies has helped us diagnose these disorders. Unfortunately, 20 percent to 30 percent of the time the genes we identify are of unknown significance. In addition, it is estimated that 25 percent to 30 percent of the genes that cause RASopathies are unidentified. These represent a challenge in confirming the clinical diagnosis for management recommendations.
Metabolomics is the study of the unique fingerprints of specific cellular processes, giving us a snapshot of the physical state of the organism and providing deeper understanding of biology and how disease alters normal processes. In this proposal, we plan to characterize the metabolomics across known RASopathies to develop a prediction test to help stratify genetic variants. We also plan to test this approach for the identification of novel genes associated with RASopathies. Our goal is to integrate metabolomics and genomics for patients with RASopathies to provide better diagnostics and patient care.